The Effect of Glitazone Treatment on Bone Marrow and Bone Marrow Cells

University of Aarhus

Status and phase: Completed; Phase 2

Conditions: Change in Bone Marrow Fat Content; Change in Bone Mineral Density

Treatments: Drug: Rosiglitazone; Drug: Placebo pill

Study type: Interventional

Funder types: Other

Identifiers

NCT00609362

2007-223

Details and patient eligibility

About

Osteoporosis is a generalised bone disease leading to an increased risk of fractures. The disease is caused partly by environmental and partly by genetic factors. It is well known that the fat content of the bone marrow is increased in osteoporotic patients. Animal studies suggest that stimulation of bone marrow stem cells through the molecule PPARgamma with the drug rosiglitazone converts the stem cells to fat cells instead of bone cells thereby decreasing bone strength. In a single study healthy volunteers were treated with rosiglitazone for 14 weeks and had a decrease in bone mineral density.

In the present study we wish to investigate the effect of this treatment on bone and fat tissue. 25 women above the age of 60 will be treated with rosiglitazone 8 mg/day for 14 weeks and compared with 25 women receiving placebo.

The effect will be evaluated as follows:

1. The effect on bone marrow density will be examined by a bone scan prior to and after treatment and again after 6 and 9 months.
2. The effect on bone turnover will be measured in blood- and urine samples at the same times.
3. The effect on fat distribution will be evaluated by an MRI scan after treatment.
4. The effect on bone marrow cells will be investigated bone marrow sampling immediately after treatment
5. The direct effect on fat will be examined by a biopsy immediately after treatment The study hypothesis is that rosiglitazone treatment decreases bone mineral density and increases bone marrow fat content. The causal molecular mechanisms will be investigated from the bone marrow and fat samples

Enrollment: 57 patients

Sex: Female

Ages: 60 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Postmenopausal women age 60-75 with no rosiglitazone allergy

Exclusion criteria

• Osteoporosis
• Diabetes
• Hyperthyroidism, untreated hypothyroidism, hyperparathyroidism
• Treatment with bone active drugs
• Low impact fracture
• Heart disease
• Kidney failure
• Liver failure
• Anaemia
• Ineligibility for MRI-scan
• Cancer within last 5 years

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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57 participants in 2 patient groups, including a placebo group

Rosiglitazone

Active Comparator group

Description:

25 women age 60 to 75 years receiving rosiglitazone 8 mg/day

Treatment:

Drug: Rosiglitazone

Placebo

Placebo Comparator group

Description:

25 women 60 to 75 years of age receiving placebo once a day for 14 weeks

Treatment:

Drug: Placebo pill